טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentRam Sigal
SubjectThe Role of Sanat Maria and Megalin in Apoptotic Cell
Clearance during Development of Drosophila
Central Nervous System
DepartmentDepartment of Medicine
Supervisor Dr. Estee Kurant
Full Thesis textFull thesis text - English Version


Abstract

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The removal of dying cells by phagocytes is a critical aspect of animal development and tissue maintenance in the adult; defects in cell corpse clearance can lead to inflammation and auto-immune diseases. Professional and non-professional phagocytes must distinguish between living and dying cells with superb level of specificity, which is achieved through function of phagocytic receptors that recognize "eat- me" signals exposed on dying cells. In mammals, phagocytic receptors are highly redundant, making it difficult to study their function in vivo. Since phagocytosis is an evolutionarily conserved process, we use the Drosophila model to uncover its molecular and cellular mechanisms. 

Development of Drosophila central nervous system (CNS) involves massive neuronal apoptosis followed by glial phagocytosis. Our lab has previously shown that two phagocytic receptors Six-Micron-Under (SIMU) and Draper (DRPR) are required for proper removal of apoptotic neurons by phagocytic glia. However, in simu;drpr double mutants, which are viable and fertile, phagocytosis of apoptotic cells in the embryonic CNS is not completely abolished, suggesting that additional players function in removal of apoptotic neurons during CNS development. In the work presented here we focused on two putative phagocytic receptors that are expressed in glial cells during late embryogenesis: CD36 receptor homolog - Santa Maria (Scavenger receptor Acting in Neural Tissue And MAjority of Rhodopsin Is Absent), and Low-density lipoprotein (LDL) receptor homolog - Megalin.

In this study we demonstrate that Santa Maria is required for glial clearance of apoptotic neurons during embryogenesis. Moreover, we show that Santa Maria and SIMU function in parallel pathways. However, it seems that Santa Maria and DRPR act in the same pathway. In addition, we show that the Santa Maria protein binds phosphatidylcholine (PC) in vitro, which may serve as a ligand on apoptotic cells. In the second part of this work we show that Megalin is not involved in glial phagocytosis of apoptotic neurons during embryogenesis.